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Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

Weng PH, Huang YL, Page JH, Chen JH, Xu J, Koutros S, Berndt S, Chanock S, Yeager M, Witte JS, Eeles RA, Easton DF, Neal DE, Donovan J, Hamdy FC, Muir KR, Giles G, Severi G, Smith JR, Balistreri CR, Shui IM, Chen YC - PLoS ONE (2014)

Bottom Line: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973).Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953).Meta-regression revealed that study type was not a significant source of between-study heterogeneity.

View Article: PubMed Central - PubMed

Affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

ABSTRACT

Background: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.

Methods: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.

Results: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.

Conclusions: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.

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Related in: MedlinePlus

TLR4 SNPs evaluated in this meta-analysis.This plot was generated by the Locusview program. The highlighted boxed SNPs were TLR4 polymorphisms explored by at least four studies. The remaining SNPs were those reported by three studies, discussed in the supplemental data.
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pone-0110569-g002: TLR4 SNPs evaluated in this meta-analysis.This plot was generated by the Locusview program. The highlighted boxed SNPs were TLR4 polymorphisms explored by at least four studies. The remaining SNPs were those reported by three studies, discussed in the supplemental data.

Mentions: Ten TLR4 SNPs had been evaluated by at least 4 included studies. The minor allele frequencies (MAF) between case and controls were shown in Table 2, along with the test for HWE in controls. Among them, three SNPs are located on 5′ untranslated region (UTR, rs2737191, rs1927914 and rs10759932), three are intronic SNPs (rs1927911, rs11536879, and rs2149356), one is non-synonymous exonic SNP (rs4986790), and three SNPs are located on 3′ UTR (rs11536889, rs7873784, and rs1554973). Another 10 TLR4 SNPs were reported by 3 studies, including one SNP located on the promoter region (rs10759930), one SNP located on 5′UTR (rs10116253), two intronic SNPs (rs11536869 and rs5030717), one non-synonymous exonic SNP (rs4986791), and five SNPs located on 3′ UTR (rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). The locations of the explored SNPs (10 SNPs with ≥4 studies, 10 SNPs with 3 studies) are shown in Figure 2. rs2149356, rs4986790 and rs7873784 in Chen's study and rs1927911 in Wang's study were out of HWE (P = 0.01–0.03) but were kept in the analysis because the HWE tests were not significant after correction for multiple tests.


Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

Weng PH, Huang YL, Page JH, Chen JH, Xu J, Koutros S, Berndt S, Chanock S, Yeager M, Witte JS, Eeles RA, Easton DF, Neal DE, Donovan J, Hamdy FC, Muir KR, Giles G, Severi G, Smith JR, Balistreri CR, Shui IM, Chen YC - PLoS ONE (2014)

TLR4 SNPs evaluated in this meta-analysis.This plot was generated by the Locusview program. The highlighted boxed SNPs were TLR4 polymorphisms explored by at least four studies. The remaining SNPs were those reported by three studies, discussed in the supplemental data.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215920&req=5

pone-0110569-g002: TLR4 SNPs evaluated in this meta-analysis.This plot was generated by the Locusview program. The highlighted boxed SNPs were TLR4 polymorphisms explored by at least four studies. The remaining SNPs were those reported by three studies, discussed in the supplemental data.
Mentions: Ten TLR4 SNPs had been evaluated by at least 4 included studies. The minor allele frequencies (MAF) between case and controls were shown in Table 2, along with the test for HWE in controls. Among them, three SNPs are located on 5′ untranslated region (UTR, rs2737191, rs1927914 and rs10759932), three are intronic SNPs (rs1927911, rs11536879, and rs2149356), one is non-synonymous exonic SNP (rs4986790), and three SNPs are located on 3′ UTR (rs11536889, rs7873784, and rs1554973). Another 10 TLR4 SNPs were reported by 3 studies, including one SNP located on the promoter region (rs10759930), one SNP located on 5′UTR (rs10116253), two intronic SNPs (rs11536869 and rs5030717), one non-synonymous exonic SNP (rs4986791), and five SNPs located on 3′ UTR (rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). The locations of the explored SNPs (10 SNPs with ≥4 studies, 10 SNPs with 3 studies) are shown in Figure 2. rs2149356, rs4986790 and rs7873784 in Chen's study and rs1927911 in Wang's study were out of HWE (P = 0.01–0.03) but were kept in the analysis because the HWE tests were not significant after correction for multiple tests.

Bottom Line: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973).Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953).Meta-regression revealed that study type was not a significant source of between-study heterogeneity.

View Article: PubMed Central - PubMed

Affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

ABSTRACT

Background: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.

Methods: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.

Results: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.

Conclusions: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.

Show MeSH
Related in: MedlinePlus